4-Methylmorpholine → CBz-D-phenylglycine 4-[l-(Boc)piperidin-4-yl]piperidinamide

HRID 2229584Notes

Reaction equation

HRID 2229584 reaction equation
[CH:1]1[CH:6]=[CH:5][C:4]([CH2:7][O:8][C:9]([NH:11][C@@H:12]([C:19]([OH:21])=[O:20])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])=[CH:3][CH:2]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[NH:37]1[CH2:42][CH2:41][CH:40]([CH:43]2[CH2:48][CH2:47][N:46]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:45][CH2:44]2)[CH2:39][CH2:38]1>C1COCC1>[CH:1]1[CH:6]=[CH:5][C:4]([CH2:7][O:8][C:9]([NH:11][C@@H:12]([C:19]([OH:21])=[O:20])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])=[CH:3][CH:2]=1.[C:49]([N:46]1[CH2:45][CH2:44][CH:43]([CH:40]2[CH2:39][CH2:38][N:37]([C:9]([NH2:11])=[O:8])[CH2:42][CH2:41]2)[CH2:48][CH2:47]1)([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 87183(R)-(((Phenylmethoxy)carbonyl)amino)phenylacetic acidHCID 117475994,4'-Bipiperidine, 1-boc protected

Product 1

HCID 131722771CBz-D-phenylglycine 4-[l-(Boc)piperidin-4-yl]piperidinamideYield 121.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of CBz-D-phenylglycine (877 mg, 3.1 mmol) in anhydrous THF (40 ml) at −25° C. was added N-methylmorpholine (336 μl, 3.1 mmol) and isobutyl chloroformate (419 μl, 3.1 mmol). The resulting suspension was left to stir for 5 min at this temperature and then the t-Butyl 4-(piperidin-4-yl)piperidine-1-carboxylate (825 mg, 3.1 mmol) in anhydrous THF (5 ml) was added in one portion at −25° C. and the reaction mixture allowed to warm to room temperature over 1 hour. The N-methylmorpholine hydrochloride was filtered off and the THF removed under vacuo. The resulting solid was treated with TFA/DCM (20 ml, 1:1) and the reaction mixture left to stir for 2 hours. The organics were removed under vacuo, the residue dissolved in ethyl acetate (100 ml), washed with aq. sodium bicarbonate solution, brine, dried and concentrated to yield the title compound as a clear oil (1.12 g, 84% over two steps).

Workup

  1. waitThe resulting suspension was left
  2. filtrationThe N-methylmorpholine hydrochloride was filtered off
  3. customthe THF removed under vacuo
  4. additionThe resulting solid was treated with TFA/DCM (20 ml, 1:1)
  5. waitthe reaction mixture left
  6. stirringto stir for 2 hours
  7. customThe organics were removed under vacuo
  8. dissolutionthe residue dissolved in ethyl acetate (100 ml)
  9. washwashed with aq. sodium bicarbonate solution, brine
  10. customdried
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-c804f129be314174bd8d191b638dd478
Source dataset
uspto-grants-2002_07
Patent number
US06420438B1

Reaction notes

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